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Journal of Virology, August 2008, p. 7725-7728, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00237-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Single Amino Acid Substitution in the Murine Norovirus Capsid Protein Is Sufficient for Attenuation In Vivo{triangledown}

D. Bailey,1,{dagger} L. B. Thackray,2,{dagger} and I. G. Goodfellow1*

Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom,1 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri2

Received 2 February 2008/ Accepted 10 May 2008

Murine norovirus (MNV), a prevalent pathogen of laboratory mice, shares many characteristics with human noroviruses. Previous results indicated that passage of MNV1 in the macrophage cell line RAW 264.7 results in attenuation in STAT1-deficient mice (C. E. Wobus, S. M. Karst, L. B. Thackray, K. O. Chang, S. V. Sosnovtsev, G. Belliot, A. Krug, J. M. Mackenzie, K. Y. Green, and H. W. Virgin, PLoS. Biol. 2:e432, 2004). Sequence analysis revealed two amino acid differences between the virulent and attenuated viruses. Using an infectious cDNA clone of the attenuated virus, we demonstrated that a glutamate-to-lysine substitution at position 296 in the capsid protein (VP1) is sufficient to restore virulence in vivo, identifying, for the first time, a virus-encoded molecular determinant of norovirus virulence.

* Corresponding author. Mailing address: Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom. Phone: 44 (0) 207 5942002. Fax: 44 (0) 207 5943973. E-mail: I.Goodfellow{at}imperial.ac.uk

{triangledown} Published ahead of print on 21 May 2008.

{dagger} These authors contributed equally to the work.

Journal of Virology, August 2008, p. 7725-7728, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00237-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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